DOCSLIB.ORG

A Common Maturation Pathway for Small Nucleolar Rnas

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Common Maturation Pathway for Small Nucleolar Rnas The EMBO Journal vol.14 no.19 pp.4860-4871, 1995 A common maturation pathway for small nucleolar RNAs Michael P.Terns1 2, Christian Grimm, mRNA (Birmstiel and Schaufele, 1988). Most nucleo- Elsebet Lund and James E.Dahlberg plasmic snRNAs are made by RNA polymerase II (RNAP II) and contain a sequence element known as the Sm site Department of Biomolecular Chemistry, 1300 University Avenue, to which the group of Sm proteins bind. After binding of University of Wisconsin, Madison, WI 53706, USA the Sm proteins to these RNAs their 5' m7G caps undergo 'Present address: Department of Biochemistry and Molecular Biology, hypermethylation to trimethylguanosine 5' cap structures. Life Sciences Building, University of Georgia, Athens, GA 30602- The spliceosomal U6 RNA, which is made by RNAP III 7229, USA does not have an m7G cap nor an Sm protein binding site. 2Corresponding author snoRNAs are synthesized by RNAP II (i.e. U3, U8 and U13) or RNAP III (i.e. 7-2/MRP and plant U3) and some We have shown that precursors of U3, U8 and U14 are processed from the intronic sequences of mRNAs (i.e. small nucleolar RNAs (snoRNAs) are not exported to U14-U22). Specific steps of pre-rRNA processing require the cytoplasm after injection into Xenopus oocyte nuclei particular snoRNAs such as U3, U8, U14, 7-2/MRP and but are selectively retained and matured in the nucleus, U22 RNAs (Tyc and Steitz, 1989; Kass et al., 1990; Li where they function in pre-rRNA processing. Our et al., 1990; Savino and Gerbi, 1990; Hughes and Ares, results demonstrate that Box D, a conserved sequence 1991; Peculis and Steitz, 1993, 1994; Morrissey and element found in these and most other snoRNAs, Tollervey, 1995). Most nucleolar RNAs contain common plays a key role in their nuclear retention, 5' cap sequence elements (Boxes C', C and D) and are associated hypermethylation and stability. Retention of U3 and with the conserved 34-36 kDa nucleolar protein fibrillarin U8 RNAs in the nucleus is saturable and relies on one (Caizergues-Ferrer et al., 1991; Tollervey et al., 1991). or more common factors. Hypermethylation of the 5' Mature snoRNAs contain either a trimethylguanosine 5' caps of U3 RNA occurs efficiently in oocyte nuclear cap structure (Tyc and Steitz, 1989) or a triphosphate 5' extracts lacking nucleoli, suggesting that precursor end (Kiss et al., 1991; Yuan and Reddy, 1991) depending snoRNAs are matured in the nucleoplasm before they on whether they are RNAP II or III gene products, are localized to the nucleolus. Surprisingly, m7G- respectively, but those that are processed from mRNA capped precursors of spliceosomal small nuclear RNAs introns contain monophosphate 5' ends (Kiss and (snRNAs) such as pre-Ul and U2, can be hypermethyl- Filipowicz, 1993; Tycowski et al., 1993). ated in nuclei if the RNAs are complexed with Sm snRNAs must undergo maturation in order to become proteins. This raises the possibility that a single nuclear functional. The nucleoplasmic snRNAs bind the common hypermethylase activity may act on both nucleolar and Sm proteins and undergo hypermethylation of their m7G spliceosomal snRNPs. cap structures after being exported to the cytoplasm Keywords: nucleolar snoRNA/nucleus/snRNA/transport/ (Mattaj, 1986). Recent evidence indicates that export of Xenopus oocyte nucleoplasmic pre-snRNAs to the cytoplasm is facilitated by interactions of specific nuclear factors with the m7G cap and sequence domains within the body of these RNAs (Izaurralde et al., 1992; Terns et al., 1993a,b; Jarmolowski Introduction et al., 1994). Likewise, import of mature snRNAs back Small nuclear RNAs (snRNAs), together with their into the nucleus is promoted by the bound Sm proteins associated proteins, are required to process precursors of and the trimethylguanosine 5' cap structures (Fischer and other cellular RNAs into mature RNA species (for review, Luhrmann, 1990; Hamm et al., 1990; Fischer et al., 1993). see Baserga and Steitz, 1993). The many different snRNAs The maturation pathways used by snoRNAs have not can be generally divided into two classes based on the been extensively studied. Despite the similarities between intranuclear location of their function. Nucleoplasmic U3 RNA and nucleoplasmic snRNAs (both are synthesized snRNAs function in pre-mRNA processing in the nucleo- in the nucleus by RNAP II with an m7G cap that later plasm (reviewed in Luhrmann et al., 1990; Green, 1991), gets hypermethylated), the maturation pathways used by whereas nucleolar snRNAs (snoRNAs) function in pre- U3 RNA and nucleoplasmic snRNAs differ significantly. rRNA processing (or ribosome biogenesis) in the nucleolus Recently, we showed that U3 RNA is not exported to the (reviewed in Filipowicz and Kiss, 1993; Fournier and cytoplasm but acquires its trimethylguanosine cap structure Maxwell, 1993; Maxwell and Foumier, 1995) in the nucleus (Tems and Dahlberg, 1994). The nucleoplasmic snRNAs include the spliceosomal In this study we show that in addition to U3 snRNA, snRNAs (i.e. Ul, U2, U4, U5 and U6 RNAs) which are other snoRNAs including U8 and U14 RNAs are matured required for intron removal from pre-mRNAs (Guthrie solely within the nucleus. We also demonstrate that Box and Patterson, 1988; Luhrmann et al., 1990) and U7 RNA D, a six nucleotide sequence element present near the 3' which is necessary for 3' end formation of histone pre- terminus of most snoRNAs (Filipowicz and Kiss, 1993; 486040 Oxford University Press Maturation of small nucleolar RNAs A T- tz > B h :---m immunoprecipitation of nuclear RNAs with antibodies N ,\ (- C- (- 1) s p s specific to the monomethyl (m7G) and trimethyl (m2'2'7G) guanosine cap structures (present on precursor and mature t-3_I snRNAs, respectively). Thus, m7G-capped precursors of tU3 ___l_ * snoRNAs such as U3 and U8 are not exported to the _2ot....ei cytoplasm but are matured solely within the nucleus. UJ2l.__. .mw1 Moreover, these RNAs were both associated with fibrillarin protein following their injection into nuclei (data not shown; Peculis and Steitz, 1994). _w. __ L'I w__ C".l_R1 ..... Structural elements needed for nuclear retention _ of snoRNAs _ To determine if the nuclear retention of U3 and U8 RNAs U8 _ _ U8X_...................8. was saturable, we assayed the nucleocytoplasmic distribu- tion of the RNAs when they were present in nuclei in high amounts. Injection of 0.1 ng of U3 DNA template resulted in accumulation ofU3 RNA only in the nucleus (Figure 2A, Fig. 1. Nuclear retention and hypermethylation of snoRNAs. lanes 1 and 2). However, injection of 10 times that amount (A) Nucleocytoplasmic distribution of U3, U2, Ul and U8 RNAs following their injection into oocyte nuclei. 32P-labeled m7G-capped of DNA, to elevate the level of U3 RNA produced, resulted U3, U2, Ul and U8 RNAs were synthesized in vitro and the RNA in the accumulation of significant amounts of U3 RNA in mixture was injected into nuclei of Xenopus oocytes. After 2 and 6 h the cytoplasm (lanes 3 and 4). Moreover, the percentage of of incubation at 18°C, the labeled RNAs present in the nuclear (N) U3 RNA that was trimethylguanosine-capped decreased and cytoplasmic (C) fractions of the oocytes were isolated and from >90% (Tems and Dahlberg, 1994) to -50% (Figure analyzed by electrophoresis in a denaturing polyacrylamide gel. Lane 1 (M) shows the RNAs prior to injection. (B) Identification of the 5' 2B, lanes 1-4) when high amounts of U3 DNA were cap structure (either m7G or m2.2'7G) by immunoprecipitation. injected. These results indicate that oocytes have a limited Precipitation was carried out with nuclear RNAs shown in lane 4 of capacity for both retaining and hypermethylating U3 (A), using anti-m7G (Munns et al., 1982) or anti-m 2'27G (Bringmann snoRNA in the nucleus. et al., 1983) cap antibodies as indicated. The RNAs present in the It is that the appearance of U3 RNA in the total sample (T), precipitate (P) and supematant (S) fractions were unlikely separated by gel electrophoresis as in (A). cytoplasm was the result of non-specific RNA leakage during oocyte fractionation since co-expressed U6 RNA (an RNA which also does not exit the nucleus) remained Foumier and Maxwell, 1993; Maxwell and Fournier, exclusively within the nucleus (Figure 2A, lanes 3 and 1995), is necessary for the efficient nuclear hypermethyl- 4). Furthermore, as shown in lanes 4 and 6, the appearance ation of these RNAs both in vivo and in vitro. The retention of U3 RNA in the cytoplasm was prevented by injection of of U3 and U8 RNAs in the nucleus is a saturable process an antibody that blocks RNA export (Terns and Dahlberg, and a common titratable factor is apparently involved in 1994; E.Lund, unpublished data) by binding to nuclear the nuclear retention of both RNAs. Box D sequences are pore glycoproteins. Essentially all of the U3 RNA that essential for the retention of U8 RNA but not U3 RNA. appeared in the cytoplasm under conditions of elevated We conclude that specific interactions between precursors U3 RNA synthesis was m7G-capped (Figure 2B, compare of snoRNAs and limiting components in the nucleus are U3 and Ul RNAs in lanes 5-8). Retention of U8 RNA responsible for retaining these RNAs in the nucleus. was also a saturable process as shown by its appearance in the cytoplasm when large amounts of the RNA were injected into nuclei (see below). Results Since both U3 and U8 RNAs are retained within the Nuclear retention and hypermethylation of capped nucleus, we tested whether they shared common saturable snoRNAs retention mechanisms. To do this we co-injected radio- To test if nuclear retention and cap hypermethylation are labeled U3 and U8 RNAs with increasing amounts of general properties of snoRNAs made by RNAP II rather these RNAs as non-radioactive competitors and monitored than specific behaviors of U3 RNA (Tems and Dahlberg, the nucleocytoplasmic distributions of radiolabeled RNAs 1994), we monitored the intracellular localization of (Figure 3A).
Load more

Recommended publications
  • Defects in the Regulation of Genome Duplication Can Lead to Cancer
    Defects in the Regulation of Genome Duplication can Lead to Cancer Susan Gerbi George Eggleston Professor of Biochemistry CURRENT RESEARCH AFFILIATION Novel models for cancer diagnosis, therapy, and Brown University prevention EDUCATION Cancer is a disease of runaway cell division. Duplication of DNA, the hereditary material, B.A. (honors) in Zoology, 1965,Barnard College must occur before cell division ensues. Therefore, understanding what regulates the initiation M.Phil., Biology, 1968,Yale University of DNA synthesis will uncover the checkpoint that regulates the onset of cell division. DNA Ph.D., in Biology, 1970,Yale University carries the blueprint of life. It is crucial that it be duplicated perfectly to pass exact copies to the daughter cells. Dr. Susan Gerbi, the George Eggleston Professor at Brown University, seeks to understand origins of DNA replication where DNA synthesis begins. Identification of AWARDS the many replication origins in the genome will elucidate the molecular mechanisms Fellow of AAAS, 2008-current regulating the initiation of DNA synthesis and the coordination of cell growth and cell division. Recipient of Rhode Island Governor’s Award for Scientific Achievement, 1993 Dr. Gerbi and her team are working to translate their findings into new modes of cancer American Society for Cell Biology diagnosis, therapy, and prevention. Her studies to get at the heart of the matter by understanding molecular mechanisms fuel her passion to translate these basic findings into improvement of human health. RESEARCH AREAS Health & Wellness, Longevity, Immortality Research Dr. Gerbi uses many models, ranging from yeast, flies, frogs, and cultured human cells, selecting the organism whose biology is best suited to address the question at hand to elucidate fundamental mechanisms.
    [Show full text]
  • 1995 Susan A. Gerbi a Native New Yorker, Susan Gerbi Attended
    1995 Susan A. Gerbi A native New Yorker, Susan Gerbi attended Barnard College, developing a particularly strong background in developmental biology, molecular genetics, and cell biology. At Barnard, John Moore and Lucinda Barth were two teachers that nurtured Gerbis growing interest in research. As a sophomore, she took J. Herbert Taylors molecular genetics course, and this confirmed her interest in eukaryotic chromosomes. During her senior year at Barnard, Gerbi did an independent research project at Columbia P&S under Reba Goodman, who introduced Gerbi to the giant polytene chromosomes of the fungus fly, Sciara coprophila. These flies were obtained from Helen Crouse, a research associate of J. Herbert Taylors, and years later upon her retirement she gave the Sciara stock center to Gerbi to maintain. The DNA puffs of Sciara chromosomes are sites of DNA amplification and provide an excellent model system to study DNA replication, a subject that had interested Gerbi since high school and which she is still actively studying. She wanted to work on DNA puffs for her Ph.D. thesis, but the time was not yet ripe, and instead she worked on Sciara ribosomal RNA (rRNA) genes. However, recently her lab has mapped a DNA puff origin of replication, which, as a result of her studies, now ranks among the best characterized metazoan origins. Her lab is now investigating regulation of this origin by the steroid hormone, ecdysone. Moving to Yale for her Ph.D., Gerbi studied under Joe Gall (both Gerbi and Gall were later to become Presidents of the ASCB). Gall remembers his young student as bright, articulate, and strongly motivated.
    [Show full text]
  • A Possible Mechanism for the Inhibition of Ribosomal RNA Gene
    Published May 1, 1995 A Possible Mechanism for the Inhibition of Ribosomal RNA Gene Transcription during Mitosis Dieter Weisenberger and Ulrich Scheer Department of Cell and Developmental Biology, Theodor-Boveri-Institute, University of Wiirzburg, Am Hubland, D-97074 Wiirzburg, Germany Abstract. When cells enter mitosis, RNA synthesis revealed that most transcripts are released from the ceases. Yet the RNA polymerase I (pol I) transcription rDNA at mitosis. Upon disintegration of the nucleolus machinery involved in the production of pre-rRNA re- during mitosis, U3 small nucleolar RNA (snoRNA) mains bound to the nucleolus organizing region and the nucleolar proteins fibrillarin and nucleolin (NOR), the chromosome site harboring the tandemly became dispersed throughout the cytoplasm and were repeated rRNA genes. Here we examine whether excluded from the NORs. Together, our data rule out rDNA transcription units are transiently blocked or the presence of "frozen Christmas-trees" at the mitotic "frozen" during mitosis. By using fluorescent in situ NORs but are compatible with the view that inactive hybridization we were unable to detect nascent pre- pol I remains on the rDNA. We propose that expres- Downloaded from rRNA chains on the NORs of mouse 3T3 and rat kan- sion of the rRNA genes is regulated during mitosis at garoo PtK2 cells. Appropriate controls showed that the level of transcription elongation, similarly to what our approach was sensitive enough to visualize, at the is known for a number of genes transcribed by pol II. light microscopic level, individual transcriptionally ac- Such a mechanism may explain the decondensed state tive rRNA genes both in situ after experimental un- of the NOR chromatin and the immediate transcrip- folding of nucleoli and in chromatin spreads ("Miller tional reactivation of the rRNA genes following spreads").
    [Show full text]
  • The Mouse Albumin Promoter and a Distal Upstream Site Are Simultaneously Dnase I Hypersensitive in Liver Chromatin and Bind Similar Liver- Abundant Factors in Vitro
    Downloaded from genesdev.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press The mouse albumin promoter and a distal upstream site are simultaneously DNase I hypersensitive in liver chromatin and bind similar liver- abundant factors in vitro Jen-Kuei Liu, Yehudit Bergman,^ and Kenneth S. Zaret^ Section of Biochemistry, Brown University, Providence, Rhode Island 02912 USA In this paper we characterize the chromatin structure and nuclear proteins associated with different transcriptional states of the mouse serum albumin gene. We found the albumin gene to be transcribed in liver at rates 1000-fold or greater than in other tissues tested. We discovered seven DNase I hypersensitive sites encompassing the albumin gene only in liver chromatin, with strong hypersensitivity at the promoter and the enhancer, which is over 10 kb upstream. Using a gel retardation assay, we found a liver nuclear protein, or set of proteins, which binds specifically to DNA of a liver-specific hypersensitive site that maps 3.5 kb upstream, between the promoter and enhancer. Footprinting, heat insensitivity, and binding competition experiments indicate that the protein(s) have characteristics similar to a heat-stable, liver-abundant protein that binds to the albumin promoter and other enhancer and promoter sequences. Finally, we asked whether the liver-specific factors that cause DNase I hypersensitivity in vivo are present concurrently at the various sites in chromatin. We devised a simple new method to reveal that in liver, individual albumin genes are hypersensitive simultaneously at the promoter, the enhancer, and the - 3.5-kb site. Thus, transcriptionally active albumin genes appear to contain tissue-abundant factors that are present at three widely spaced points in chromatin, yet at the same point in time.
    [Show full text]
  • Frontiers in Science
    MBL Non-profit Org. U.S. Postage Biological Discovery in Woods Hole Biological Discovery in Woods PAID Plymouth, MA Permit # 55 MBL 7 MBL Street Woods Hole, MA 02543 • Frontiers in Science A NNUAL R EPORT 2007 EPORT ANNUAL REPORT 2007 Founded in 1888 as the Marine Biological Laboratory About the cover: Live endothelial cell spreading on a glass surface. Birefringence image recorded with the LC-PolScope, a microscopy technique invented at the MBL (see page 12-13). Image brightness corresponds to magnitude, color to orientation of birefringence (no stains or labels were applied to the cell.) Credit: K. Patel. The Marine Biological Laboratory does not discriminate in employment or in access to any of its The MBL Annual Report is published by the activities or programs or take any retaliatory action on the basis of race, color, religion, sex, sexual Marine Biological Laboratory. Although the orientation, national origin, ancestry, age, marital status, pregnancy, physical or mental disability, greatest possible care has been taken in the veteran status or genetic predisposition. In addition, the MBL is committed to the prevention and preparation of this record, the MBL recognizes elimination of sexual harassment, as well as other forms of unlawful harassment, in the workplace. the possibility of omissions or inaccuracies. If Through training programs and disseminated information, MBL strives to educate its employees, any are noted, please accept our apology and students, faculty, and visitors on these important issues. advise us of any corrections
    [Show full text]
  • Nuclear Organization & Function
    Abstracts of papers presented at the LXXV Cold Spring Harbor Symposium on Quantitative Biology NUCLEAR ORGANIZATION & FUNCTION June 2–June 7, 2010 CORE Metadata, citation and similar papers at core.ac.uk Provided by Cold Spring Harbor Laboratory Institutional Repository Cold Spring Harbor Laboratory Cold Spring Harbor, New York Abstracts of papers presented at the LXXV Cold Spring Harbor Symposium on Quantitative Biology NUCLEAR ORGANIZATION & FUNCTION June 2–June 7, 2010 Arranged by Terri Grodzicker, Cold Spring Harbor Laboratory David Spector, Cold Spring Harbor Laboratory David Stewart, Cold Spring Harbor Laboratory Bruce Stillman, Cold Spring Harbor Laboratory Cold Spring Harbor Laboratory Cold Spring Harbor, New York This meeting was funded in part by the National Institute of General Medical Sciences, a branch of the National Institutes of Health. Contributions from the following companies provide core support for the Cold Spring Harbor meetings program. Corporate Sponsors Agilent Technologies AstraZeneca BioVentures, Inc. Bristol-Myers Squibb Company Genentech, Inc. GlaxoSmithKline Hoffmann-La Roche Inc. Life Technologies (Invitrogen & Applied Biosystems) Merck (Schering-Plough) Research Laboratories New England BioLabs, Inc. OSI Pharmaceuticals, Inc. Sanofi-Aventis Plant Corporate Associates Monsanto Company Pioneer Hi-Bred International, Inc. Foundations Hudson-Alpha Institute for Biotechnology Cover: Top left: S. Boyle, MRC Genetics Unit, Edinburgh, UK. Top right: K.V. Prasanth, Cold Spring Harbor Laboratory. Bottom left: P.A.
    [Show full text]
  • 1996 Virginia Zakian Biology Caught Ginger Zakian's Imagination in the Ninth Grade and She Decided at That Time to Become A
    1996 Virginia Zakian Biology caught Ginger Zakian’s imagination in the ninth grade and she decided at that time to become a scientist. After graduating from high school in a Philadelphia suburb as class valedictorian, Zakian attended Cornell University. She recalls that after 12 years of boredom, Cornell was "fantastic, I thought I had gone to heaven." During her freshman year, she was even able to do research in behavioral biology, studying the effects of crowding on guppy behavior. (One of the side benefits of this research was that it exempted her from the nightly curfew to which all female undergraduates were subject.) Her undergraduate research advisor was Tonie Blackler who was "the first teacher to challenge me academically." The first semester she worked in his lab, Blackler gave her a B+, not because she hadn't worked hard or well but because he felt she was 'intellectually lazy'. Presumably as planned, Blacker's lesson stayed with Zakian and motivated her to work harder. Zakian graduated cum laude in Biology in 1970. Following Cornell, Zakian moved to Yale because it had an excellent developmental biology program, a field that she thought she wanted to pursue. After a year of sampling various labs and not finding what she wanted, Joe Gall returned from sabbatical to Yale. The day he returned, Zakian and two other students were camped outside his door hoping to join his lab. Gall, unable to choose among them, took all three (the other two were Sharyn Endow and Patricia Pukkila). In Gall’s lab, Zakian worked on the replication of satellite DNA and was introduced to the wonders and complexity of eukaryotic chromosomes.
    [Show full text]
  • 2008 Summer Undergraduate Research Fellows Conference
    22000088 SSUMMER UUNDERGRADUATE RRESEARCH FFELLOWS CCONFERENCE Monday, August 4, 2008 9:00 AM THE RYAN CENTER, UNIVERSITY OF RHODE ISLAND Supported by RI-INBRE & RI EPSCOR SUMMER UNDERGRADUATE RESEARCH FELLOWS CONFERENCE MONDAY, AUGUST 4, 2008 RYAN CENTER CONCOURSE UNIVERSITY OF RHODE ISLAND, KINGSTON 9:00 – 9:45 CONTINENTAL BREAKFAST & GROUP A POSTER SET-UP 9:45 – 10:00 WELCOME PRESIDENT ROBERT CAROTHERS, UNIVERSITY OF RHODE ISLAND DR. ZAHIR SHAIKH, RI-INBRE PROGRAM DIRECTOR DR. JEFFREY SEEMAN, RI EPSCOR PROJECT DIRECTOR 10:00 – 11:30 SUMMER UNDERGRADUATE RESEARCH FELLOWS POSTER SESSION GROUP A (POSTER #’S 1 – 41) 11:30 – 12:30 LUNCH & GROUP B POSTER SET-UP 12:30 – 2:00 SUMMER UNDERGRADUATE RESEARCH FELLOWS POSTER SESSION GROUP B (POSTER #’S 42 – 81) LIST OF STUDENT POSTERS **Please note that the poster numbers listed in the following tables also correspond with the page numbers in the abstract book. When reading the individual abstracts, the Summer Research Fellow is underlined. University of Rhode Island Poster # Summer Fellow Mentor 21 Delia Daza David Rowley, Ph.D. 22 Audrey DiRaimo Paul Cohen, Ph.D. 78 Catharine Donahue Carol Thornber, Ph.D. 32 Andrea Hodgson Matthew Stoner, Ph.D. 35 Jacqueline Jeha Kerry LaPlante, Pharm. D. 79 Caroline Killian Navindra Seeram, Ph.D. 37 Fred Kolling IV Niall Howlett, Ph.D. 39 Christopher Lee Peter Paton, Ph.D. Elizabeth DeCelles, Ph.D. 40 Jessica Lehmann Keykavous Parang, Ph.D. 41 Sara Linden Zahir Shaikh, Ph.D 42 Wendy Lopez William Euler, Ph.D. 46 Melissa Martin Robert Rodgers, Ph.D. 47 Kevin McConeghy Kerry LaPlante, Pharm.
    [Show full text]
  • 2011 Fall Sonneborn Program.Indd
    Indiana University Department of Biology Fall 2011 Sonneborn Lecture Joseph G. Gall has been a staff scientist at the Carnegie Institution’s Department of Embryology and an adjunct professor at Johns Hopkins University since 1983. The following year, he was given a lifetime appointment as an American Cancer Society Professor of Developmental Genetics. Much of his career has been spent studying how the structure of the cell, particularly the nucleus, is related to the synthesis and processing of ribonucleic acid, RNA, during gene activity. Gall earned two Zoology degrees from Yale University: a B.S. in 1949 and a Ph.D. in 1952. His doctoral work was done with Drosophila geneticist and developmental biologist Donald F. Poulson. After graduation, Gall accepted a teaching position at the University of Minnesota where he became a Professor of Zoology. He returned to Yale in 1963, accepting a position as Professor of Molecular Biophysics and Biochemistry. His last position at Yale was as the Ross G. Harrison Chair in Biology. Gall has been a member of the American Society for Cell Biology, serving as the organization’s president from 1967-1968. His in situ hybridization technique, developed with graduate students Mary Lou Pardue and Susan Gerbi in 1969, is a powerful method that allows researchers to locate and map genes and specifi c sequences of DNA on a chromosome. This technique revolutionized molecular biology and is now Photo courtesy of the Carnegie Institution for Science used worldwide in gene studies. In 2006, Gall was honored with the Albert Lasker Award for Special Achievement in Medical Science.
    [Show full text]
  • Eukaryotic Dna Replication & Genome Maintenance
    Abstracts of papers presented at the 2011 meeting on EUKARYOTIC DNA REPLICATION & GENOME MAINTENANCE September 6–September 10, 2011 View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Cold Spring Harbor Laboratory Institutional Repository Cold Spring Harbor Laboratory Cold Spring Harbor, New York Abstracts of papers presented at the 2011 meeting on EUKARYOTIC DNA REPLICATION & GENOME MAINTENANCE September 6–September 10, 2011 Arranged by Stephen Bell, HHMI / Massachusetts Institute of Technology Joachim Li, University of California, San Francisco Johannes Walter, Harvard Medical School Cold Spring Harbor Laboratory Cold Spring Harbor, New York This meeting was funded in part by the National Cancer Institute, a branch of the National Institutes of Health; and the National Science Foundation. Contributions from the following companies provide core support for the Cold Spring Harbor meetings program. Corporate Sponsors Agilent Technologies Astellas-OSI Oncology AstraZeneca BioVentures, Inc. Bristol-Myers Squibb Company Genentech, Inc. GlaxoSmithKline Life Technologies (Invitrogen & Applied Biosystems) New England BioLabs, Inc. Sanofi-Aventis Plant Corporate Associates Monsanto Company Pioneer Hi-Bred International, Inc. Foundations Hudson-Alpha Institute for Biotechnology ________________________________________________________________ Cover: Sulfolobus Orc1-1 and Orc1-3 bound to DNA. Photo courtesy of James Berger. EUKARYOTIC DNA REPLICATION & GENOME MAINTENANCE Tuesday, September 6 – Saturday, September
    [Show full text]
  • Susan Gerbi CV
    January 2016 For External Use CURRICULUM VITAE OF SUSAN A. GERBI, PH.D. TABLE OF CONTENTS PAGE Education, Appointments ........................................................................................................................................ 2 Honors .................................................................................................................................................................... 3 Extramural Grants ................................................................................................................................................. 4-7 Publications ......................................................................................................................................................... 8-24 Invited Seminars ................................................................................................................................................ 24-29 Service to the University, Profession & Community .......................................................................................... 29-35 Membership and Service in Professional Societies ………………………………………………………………….35-36 Teaching ............................................................................................................................................................ 36-44 Susan A. Gerbi CURRICULUM VITAE 1. Name: Susan Alexandra Gerbi Birth: New York, New York Married: Prof. James Terrell McIlwain, M.D. 2. Home Address: 37 Medalist Drive Rehoboth, Massachusetts 02769, USA (774) 565-0353 3.
    [Show full text]
  • Distinct Epigenetic Features of Differentiation-Regulated Replication
    Smith et al. Epigenetics & Chromatin (2016) 9:18 DOI 10.1186/s13072-016-0067-3 Epigenetics & Chromatin RESEARCH Open Access Distinct epigenetic features of differentiation‑regulated replication origins Owen K. Smith1, RyanGuk Kim2, Haiqing Fu1, Melvenia M. Martin1, Chii Mei Lin1, Koichi Utani1, Ya Zhang1, Anna B. Marks1, Marc Lalande3, Stormy Chamberlain3, Maxwell W. Libbrecht4, Eric E. Bouhassira5, Michael C. Ryan2, William S. Noble4,6 and Mirit I. Aladjem1* Abstract Background: Eukaryotic genome duplication starts at discrete sequences (replication origins) that coordinate cell cycle progression, ensure genomic stability and modulate gene expression. Origins share some sequence features, but their activity also responds to changes in transcription and cellular differentiation status. Results: To identify chromatin states and histone modifications that locally mark replication origins, we profiled ori- gin distributions in eight human cell lines representing embryonic and differentiated cell types. Consistent with a role of chromatin structure in determining origin activity, we found that cancer and non-cancer cells of similar lineages exhibited highly similar replication origin distributions. Surprisingly, our study revealed that DNase hypersensitivity, which often correlates with early replication at large-scale chromatin domains, did not emerge as a strong local deter- minant of origin activity. Instead, we found that two distinct sets of chromatin modifications exhibited strong local associations with two discrete groups of replication origins. The first origin group consisted of about 40,000 regions that actively initiated replication in all cell types and preferentially colocalized with unmethylated CpGs and with the euchromatin markers, H3K4me3 and H3K9Ac. The second group included origins that were consistently active in cells of a single type or lineage and preferentially colocalized with the heterochromatin marker, H3K9me3.
    [Show full text]